Christoph B Olivier1,2, Vandana Sundaram3, Glenn M Chertow4, Sumana Shashidhar1, Lori K McDonnell5, Victoria Y Ding3, Manisha Desai3, Kenneth W Mahaffey1, Matthew Mell5,6. 1. Stanford Center for Clinical Research (SCCR), Department of Medicine, School of Medicine, Stanford University, Stanford, CA, USA. 2. Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center, University of Freiburg, Freiburg, Germany. 3. Quantitative Sciences Unit, Department of Medicine, School of Medicine, Stanford University, Stanford, CA, USA. 4. Division of Nephrology, School of Medicine, Stanford University, Stanford, CA, USA. 5. Division of Vascular Surgery, School of Medicine, Stanford University, Stanford, CA, USA. 6. Division of Vascular Surgery, University of California at Davis, Sacramento, CA, USA.
Abstract
BACKGROUND: Protease-activated receptor-1 antagonism by vorapaxar could facilitate arteriovenous fistula maturation but may increase bleeding risk. OBJECTIVE: The primary objective of the Vorapaxar Study for Maturation of arteriovenous fistula for Hemodialysis Access (VorapAccess) was to determine if vorapaxar improves arteriovenous fistula functional maturation in patients with end-stage renal disease. METHODS: VorapAccess was a randomized, placebo-controlled, double-blind pilot trial comparing 2.5 mg vorapaxar per day with placebo for twelve weeks starting on day two after arteriovenous fistula creation. The primary outcome was time to functional maturation defined as successful cannulation for six hemodialysis sessions within three weeks. The planned sample size was 50 participants. The study was terminated early after withdrawal of planned financial support. Given the small number of randomized patients, we performed descriptive analyses without inference testing. RESULTS: A total of 13 participants were randomly allocated study drug (six vorapaxar and seven placebo). The median age was 56 years and seven participants (54%) were female. The median (minimum-maximum) days to functional maturation were 169 (77-287) days in the vorapaxar group and 145 (48-198) days in the placebo group. Six of the 13 (46%) participants had arteriovenous fistula functional maturation within 180 days; two of six (33%) in the vorapaxar group and four of seven (57%) in the placebo group. There was one bleeding event in the placebo group. CONCLUSION: Fewer than half of participants had functional maturation within 180 days after surgery, suggesting a major need for agents or strategies that enhance arteriovenous fistula maturation.
BACKGROUND: Protease-activated receptor-1 antagonism by vorapaxar could facilitate arteriovenous fistula maturation but may increase bleeding risk. OBJECTIVE: The primary objective of the Vorapaxar Study for Maturation of arteriovenous fistula for Hemodialysis Access (VorapAccess) was to determine if vorapaxar improves arteriovenous fistula functional maturation in patients with end-stage renal disease. METHODS: VorapAccess was a randomized, placebo-controlled, double-blind pilot trial comparing 2.5 mg vorapaxar per day with placebo for twelve weeks starting on day two after arteriovenous fistula creation. The primary outcome was time to functional maturation defined as successful cannulation for six hemodialysis sessions within three weeks. The planned sample size was 50 participants. The study was terminated early after withdrawal of planned financial support. Given the small number of randomized patients, we performed descriptive analyses without inference testing. RESULTS: A total of 13 participants were randomly allocated study drug (six vorapaxar and seven placebo). The median age was 56 years and seven participants (54%) were female. The median (minimum-maximum) days to functional maturation were 169 (77-287) days in the vorapaxar group and 145 (48-198) days in the placebo group. Six of the 13 (46%) participants had arteriovenous fistula functional maturation within 180 days; two of six (33%) in the vorapaxar group and four of seven (57%) in the placebo group. There was one bleeding event in the placebo group. CONCLUSION: Fewer than half of participants had functional maturation within 180 days after surgery, suggesting a major need for agents or strategies that enhance arteriovenous fistula maturation.
Authors: Laura M Dember; James S Kaufman; Gerald J Beck; Bradley S Dixon; Jennifer J Gassman; Tom Greene; Jonathan Himmelfarb; Lawrence G Hunsicker; John W Kusek; Jeffrey H Lawson; John P Middleton; Milena Radeva; Steve J Schwab; James F Whiting; Harold I Feldman Journal: Clin Trials Date: 2005 Impact factor: 2.486
Authors: Ke Wang; Leila R Zelnick; Peter B Imrey; Ian H deBoer; Jonathan Himmelfarb; Michael D Allon; Alfred K Cheung; Laura M Dember; Prabir Roy-Chaudhury; Miguel A Vazquez; John W Kusek; Harold I Feldman; Gerald J Beck; Bryan Kestenbaum Journal: Am J Nephrol Date: 2018-08-02 Impact factor: 3.754
Authors: Claudia K Derian; Bruce P Damiano; Michael F Addo; Andrew L Darrow; Michael R D'Andrea; Mark Nedelman; Han-Cheng Zhang; Bruce E Maryanoff; Patricia Andrade-Gordon Journal: J Pharmacol Exp Ther Date: 2003-02 Impact factor: 4.030
Authors: L Nieuwenhuizen; W J J Falkenburg; R E G Schutgens; G Roosendaal; K van Veghel; D H Biesma; F P J G Lafeber Journal: Scand J Immunol Date: 2013-05 Impact factor: 3.487
Authors: Mark A Crowther; Catherine M Clase; Peter J Margetts; Jim Julian; Kim Lambert; Denise Sneath; Ryuta Nagai; Sarah Wilson; Alistair J Ingram Journal: J Am Soc Nephrol Date: 2002-09 Impact factor: 10.121